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Biomedical subjects

S A Clark

Publications and source records attributed to S A Clark.

At least 37 records · Page 2Linked to original sources

Binding of angiotensin antagonists to rat liver and brain membranes measured ex vivo.

1. The effects of the angiotensin antagonists GR117289, losartan and Sar1Ala8-angiotensin II on the ex vivo binding of [125I]-Sar1Ile8-angiotensin II to rat liver and cortex/hippocampus (Cx/H) membranes have been investigated. 2. GR117289 (0.1-30 mg kg-1, s.c., 2 h pretreatment) caused a dose-dependent reduction in [125I]-Sar1Ile8-angiotensin II binding to both liver and cortex/hippocampus membranes. 3. Administration of a submaximal dose of GR117289 (1 mg kg-1, s.c.) indicated that the peak inhibition of binding in the liver occurred within 0.5 h, whereas the peak inhibition of binding in the Cx/H occurred 2 h after drug treatment. 4. The effect of GR117289 was long lasting. Binding was still reduced in the Cx/H 48 h after drug treatment (10 mg kg-1, s.c.) but had returned to normal 72 h after drug treatment. In the liver binding was still reduced 72 h after treatment with the same dose. 5. Losartan (1-30 mg kg-1, s.c.) was equipotent with GR117289 in its ability to reduce liver binding, but was less effective at inhibiting binding to central receptors. 6. The non-peptide antagonist Sar1Ala8-angiotensin II (3 and 10 mg kg-1) reduced binding in the liver but not in the Cx/H membranes. 7. These results suggest that, unlike the peptide antagonist Sar1Ala8-angiotensin II, the non-peptide angiotensin antagonists, GR117289 and losartan, are able to cross the blood brain barrier and occupy central angiotensin II receptors.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Matricide: the schizophrenic crime?

The aim of the study was to further examine the view that matricide is 'the schizophrenic crime' (Gilles, 1965). This report represents a comprehensive, retrospective and national study of all individuals in Scotland who, between 1957 and 1987 inclusive, were charged with the murder or the culpable homicide of their biological mother. Files of High Court indictments were examined for the relevant years to identify offenders prior to disposal, and individuals were followed up with respect to diagnosis and disposal. Twenty-six (twenty-three men and three women) were convicted of the murder or culpable homicide of their biological mother. Only 50 per cent (thirteen subjects) were known to the State Hospital, Carstairs. Six (24 per cent) subjects suffered from schizophrenia, seven (24 per cent) were given no diagnosis, five (20 per cent) suffered from personality disorder, four (16 per cent) from the alcohol dependence syndrome, three (12 per cent) from depressive illness, and one (4 per cent) from hypomania. Thus, whilst schizophrenia is over-represented in this subgroup of offenders, matricide should not be viewed as the schizophrenic crime. Given the prevalence of mental disorder in this group, pre-trial assessment by a Forensic Psychiatrist should be mandatory.

Adolescent↗

Problems unique to microsurgical epididymovasostomy. Comparison of four techniques in a laboratory rat model with review of the literature.

The new microsurgical techniques, tubule and loop intussusception, are compared to end-to-end and side-to-end in an experimental rat model. Sixty adult male Sprague-Dawley rats were operated on bilaterally under the same conditions. The four microsurgical techniques differ in approach to the inner mucosal layer, while the outer adventitial layer was sutured similarly in all cases. Luminal patency was checked 3 months postoperatively. There was no statistically significant difference in the patency rate among these four techniques (P = 0.3196). However, the incidence of macroscopically (P < 0.001) and microscopically (P < 0.01) detected spermatic granulomas was highly significant despite the optimum size match for each method. We found side-to-end techniques superior and easier to perform than end-to-end. The loop intussusception offers the highest patency rate (100%) with the lowest incidence of spermatic granuloma (10%). It was, therefore, concluded that selection of surgical technique is of utmost importance for durability of anastomosis.

Anastomosis, Surgical↗

The effect of contact lens cleaners on lens parameters and surface quality of the Novalens.

The purpose of this study is to evaluate the effect of one abrasive cleaner, one non-abrasive cleaner and one non-abrasive alcohol-based cleaner on the lens parameter stability of the NOVALENS. Twenty-four lenses, all NOVALENS material of identical design, were cleaned 100 times each. Eight lenses were cleaned with MiraFlow (CIBA Vision), eight lenses with Optic-Free Daily Cleaner and eight lenses with the Gas Permeable Daily Cleaner (PBH). The base curve radius, center thickness and power were verified immediately before, immediately after and (per manufacturer's recommendation) 4 hours after cleaning at baseline, 25, 50, 75 and 100 cleanings. Lens toricity of approximately 0.50D was found with all three cleaners after 100 cleanings. No change in lens power or center thickness was found. It was concluded that extreme care must be taken in handling the NOVALENS due to the potential of induced warpage.

Contact Lenses↗

Multilocus DNA fingerprint analysis of cell banks: stability studies and culture identification in human B-lymphoblastoid and mammalian cell lines.

The technique of multilocus DNA fingerprinting has great potential for the authentication of animal cell cultures and in identification of cross-contamination. The Alec Jeffreys probes 33.6 and 33.15 were used as multilocus probes to demonstrate the consistent DNA fingerprint profiles in human peripheral blood and its derivative Epstein-Barr virus (EBV) transformed B-lymphoblastoid cultures maintained by repeated subculture for six months. However, fingerprint analysis of EBV transformed cultures generated from small numbers of cells showed that the majority (seven of eight cultures) had anomalous profiles. Some of these altered profiles shared common features not seen in the peripheral blood pattern. Analysis of seven murine hybridoma clones from a single fusion experiment revealed only two clones which could not be distinguished using probe 33.15. Further studies of master and distribution cell banks for eleven cell lines demonstrated consistent fingerprint profiles in all cases except one (U937). However, this cell line showed only minor differences in the master and distribution bank profiles. These data indicate that, while changes in fingerprint profile may be identified in exceptional instances, the multilocus fingerprinting method using probes 33.6 and 33.15 is a powerful and reliable tool in the quality control of animal cell cultures.

Animals↗

MMPI-ER two-point codes of industrially injured Hispanic workers by DSM-III--R diagnosis.

The purpose of this study was to describe the MMPI-ER two-point codes of 492 Hispanic adults who had sustained work-related injuries and who had applied for workers' compensation benefits. More specifically, the focus was on whether there are unique MMPI two-point codes for Hispanic workers with three specific types of DSM-III--R diagnoses--adjustment disorder, anxiety disorder, and major depression. Analysis suggests that psychiatric condition or diagnosis may act as a moderator variable in Hispanic persons' MMPI performance, including MMPI two-point codes.

Accidents, Occupational↗

Production and characterization of monoclonal antibodies to outer membrane proteins of Pseudomonas aeruginosa grown in iron-depleted media.

The iron uptake systems of pathogenic bacteria provide potential targets for immunological intervention. We have partially purified the high molecular mass, iron-regulated outer membrane proteins (IROMPs) from Pseudomonas aeruginosa and used them to prepare a panel of monoclonal antibodies (mAbs). Five mAbs reacted with an 85 kDa IROMP separated by SDS-PAGE, but gave only low-level binding to whole cells by immunogold electron microscopy. However, iodination of whole cells indicated that the 85 kDa IROMP is surface-exposed. The mAbs were only cross-reactive with clinical isolates representing eight of the 17 International Antigenic Typing Scheme serotypes of P. aeruginosa, suggesting significant heterogeneity with respect to this IROMP.

Antibodies, Bacterial↗

Microsurgical epididymovasostomy by loop intussusception. A new technique in the rat model.

A new technique, epididymal loop intussusception into the vas deferens, is offered as an improved form compared with the side-to-end method. Loop intussusception has been experimentally studied bilaterally in 15 adult male rats. This report provides details of the technique. A 3-month anatomical and histological follow-up showed a 100% patency rate, no anastomotic stricture, and reabsorption of the blind intussuscepted loop in all but 3 cases. Macroscopic sperm granulomas were present in only 10% of the anastomoses examined. Advantages and disadvantages of microsurgical epididymovasostomy techniques are discussed.

Anastomosis, Surgical↗

Reorganization of somatosensory area 3b representations in adult owl monkeys after digital syndactyly.

1. These experiments were designed to test the hypothesis that temporally correlated afferent input activity plays a lifelong role in the establishment and modification of receptive fields (RFs) and representational topographies in the primary somatosensory cortex of adult monkeys. They were based in part on the finding that adjacent digits of the hand are represented discontinuously in area 3b of the adult owl monkey. If cortical receptive fields and the details of cortical topographic representations are shaped by the weights of the temporal correlations among afferent inputs, then representational discontinuities between digits would be expected to arise because inputs from the skin surfaces of adjacent digits are largely independent in the critical time domain. 2. In the present experiments, the skin of adjacent digits 3 and 4 of the monkey hand was surgically connected to create an artificial syndactyly, or webbed-finger condition. Highly detailed microelectrode maps of the cortical representation of the syndactyl digits were obtained 3-7.5 mo later. This experimental manipulation greatly increased the amount of simultaneous or nearly simultaneous input from the normally separated, now fused, surfaces of adjacent fingers. 3. Cortical maps of the representations of finger surfaces were highly modified from the normal after a several-month-long period of digital fusion. Specifically, the normal discontinuity between the cortical representations of adjacent fingers was abolished. Within a wide cortical zone, RFs were defined that extended across the line of syndactyly onto the surgically joined skin of both fused digits. The representational topography of the fused digits was similar to any normal single digit and was characterized by a continuous progression of partially overlapping RFs. 4. Control observations revealed that these reorganizational changes cannot be accounted for by any changes in cutaneous innervation induced by the surgery. They must arise from representational changes in the central somatosensory system. 5. These findings reveal that cortical maps can be altered in detail in adult monkeys by modifying the distributed temporal structure of afferent inputs. They support the longstanding hypothesis that the temporal coincidence of inputs plays a role in the grouping of input subsets into specific cortical RFs and, consequently, in the shaping of selected effective cortical inputs and representational topographies throughout life.

Animals↗

Microsurgical epididymovasostomy by tubule intussusception: a new technique in rat model.

This experimental study on 15 adult male rats with bilateral epididymovasostomies evaluates a new technique of tubule intussusception as an improved form of end-to-end anastomosis. This paper describes in detail the steps in this technique and offers physiological, anatomical, and histological follow-up after 3 months. With this technique there is a 97% patency rate and a 23.3% incidence of macroscopic spermatic granuloma. Complications are discussed in detail.

Animals↗

Islet cell culture in defined serum-free medium.

A serum-free, hormone- and factor-supplemented, defined medium was developed which maintains functional activity of primary cultures of adult islet cells and continuous islet cell lines. Medium supplements examined included proteose peptone (PP), transferrin (TrFe), insulin-like growth factor-I (IGF-I), an insulinotropic fragment of human GH [hGH-(6-13)], ethanolamine (EA), phosphoethanolamine (PEA), and human serum albumin (HSA). Glucose-stimulated insulin secretion from islet monolayers was determined after culture in serum-free supplemented medium by either 2- to 3-h static incubations or in a superfusion system with either low (2.8-8.3 mM) or stimulatory (16.7-19.4 mM) glucose concentrations. Glucose-induced secretion was not sustained after 3-4 days of culture in medium supplemented with PP (0.5 mg/ml) and TrFe (10 micrograms/ml) alone. Addition of T3 did not restore glucose-induced secretion, although a combination of T3 and IGF-I or of T3, IGF-I, and PRL (10(-10)-10(-9) M) maintained glucose-induced insulin secretion for 1 month. No beneficial effects were noted with hGH-(6-13). The beta-cell lines HIT-T15 and RINr 1046-38 were used to screen for a potential replacement for PP, the undefined component of the serum-free medium. A combination of HSA (1 mg/ml), EA (50 microM), and PEA (50 microM) provided a replacement for PP. In fact, insulin secretion from HIT-T15 cells was significantly better after culture in medium supplemented with HSA, EA, PEA, TrFe, T3, IGF-I, and PRL than in medium with PP, TrFe, T3, IGF-I, and PRL. HSA (1 mg/ml), EA (50 microM), and PEA (50 microM) in combination with TrFe (10 micrograms/ml), T3 (0.1 nM), IGF-I (0.65 nM), and PRL (1 nM) were used in studies with primary islet monolayers. After 3 weeks of culture islet monolayers were superfused, and the biphasic glucose-induced insulin secretion of cells maintained in defined medium was indistinguishable from the insulin secretion of cells maintained in medium with 5% fetal bovine serum. These studies indicate that adult rat beta-cells retain biphasic glucose-induced insulin secretion after extended culture in defined serum-free medium. The defined medium was also useful for cultures of RINr 1046-38 and HIT-T15 cells and should provide a basis for formulating media for islet cells from higher mammals, including man.

Animals↗

Modulation of glucose-induced insulin secretion from a rat clonal beta-cell line.

The present studies demonstrate that the beta-cell line RINr1046-38 (RIN-38) retains the capability to secrete insulin in response to glucose. The maximal effect of glucose was a 5- to 9-fold stimulation of insulin secretion from RIN-38 cells. This glucose-induced insulin secretion was maximal at 0.6 mM and was modulated by other secretagogues. Potassium concentrations of 10 mM, adenylate cyclase activators (glucagon-like peptide-1 and forskolin), and a phosphodiesterase inhibitor (isobutylmethylxanthine) potentiated glucose-induced insulin secretion, but had little or no effect on insulin secretion in the absence of glucose. Potassium concentrations of 20 mM or more, glibenclamide, and carbachol (Cch) stimulated insulin secretion 8- to 12-fold in the absence of glucose, while only Cch potentiated the effect of glucose on insulin secretion. Amino acids (alanine, arginine, leucine, and ketoisocaproate) also stimulated insulin secretion. The alpha 2-adrenergic agonist clonidine (1 microM), low extracellular calcium (less than or equal to 0.5 mM), and extended culture of RIN-38 cells at low glucose concentrations (0.33 mM) inhibited the stimulatory effect of glucose on insulin secretion. Insulin secretion was retained in RIN-38 cells for up to 98 passages. However, extended passage was associated with a decline in cellular insulin content (83% decline over 89 passages). In addition, high passage cells lost the ability to secrete insulin in response to glucose, but continued to respond to other secretagogues (K+, alanine, and carbachol). In fact, in the absence of glucose the effect of Cch on insulin secretion was well maintained in high passage cells (8- and 9.9-fold increase in insulin secretion, passages 9 and 70, respectively). Thus, low passage RIN-38 cells secrete insulin in response to glucose and other insulin secretagogues. High passage cells do not respond to glucose, but continue to respond to other secretagogues. Based on these results we propose that high and low passage RIN-38 cells provide a model for examining molecular mechanisms of glucose-induced insulin secretion. In addition, these findings emphasize that passage information is essential for interpretation of secretion studies with RIN cell lines.

1-Methyl-3-isobutylxanthine↗

Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry.

The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2-3 microns in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.

Acid Phosphatase↗

Aqueous dissolution of crystalline and amorphous amylose-alcohol complexes.

Complexes of amylose, the linear starch polysaccharide, with linear alcohols having chain lengths varying from 4 to 8 carbon atoms, were prepared. Either crystalline or amorphous complexes could be formed depending on preparation conditions. Crystalline complexes gave sharp X-ray diffraction patterns, characteristic of the VH form of amylose, whereas no observable pattern was obtained from the amorphous form. Thermal dissociation of the complexes occurred at increasing temperatures with increasing alcohol chain length. Crystalline complexes dissociated at temperatures approximately 23 degrees C higher than their amorphous counterparts and the enthalpy of dissociation was also greater for the crystalline samples. Enthalpy values were independent of alcohol chain length. Differences in thermal behaviour of the two types of complex may be described in terms of the polymer crystal lattice energy and may explain the variability of reported results for complex dissociation in the literature.

Alcohols↗

Adverse effects of a high-glucose diet on body weight and plasma calcium and 1,25-dihydroxyvitamin D3 levels in calcium-deficient growing rats.

We tested the hypothesis that dietary calcium would lead to greater impairment of body weight gain and calcium homeostasis if rats are fed a diet with a high glucose content compared with our standard diet in which the carbohydrate is supplied by whole wheat flour. Groups of female rats at 21 days of age were given either of two equivalent calcium-deficient diets with carbohydrate supplied either by glucose (LCaG) or by wheat flour (LCaW). Control rats were fed the wheat-flour diet containing 0.4% calcium. Since previous studies indicated divergent effects of glucose-based and flour-based diets on body weight in vitamin D-deficient rats, we designed a parallel study with vitamin D-deprived rats. Compared with rats fed the LCaW diet, the rats fed the LCaG diet had inferior body weight gain and more severe hypocalcemia (1-2 mg/ml lower) over a 40-day period, and no significant elevation of the plasma 1,25(OH)2D3 level at 61 days of age. Rats fed the LCaW diet maintained a 3-fold elevation of plasma 1,25(OH)2D3 relative to the level of control rats fed the 0.4% calcium diet. The dry weight and percent ash of tibias were similarly reduced in the two calcium-restricted groups compared to the control group. Among the vitamin D-deprived rats, those fed the glucose diet had poorer weight gain than those fed the wheat flour diet. However, both groups had similarly depressed serum calcium level, tibia ash content and 1,25(OH)2D3 level. Thus, a glucose diet combined with calcium restriction or vitamin D deprivation appears to accentuate the impairment of body weight gain and, when combined with calcium restriction, it also accentuates the impairment of calcium homeostasis and interferes with the adaptive increase in plasma 1,25(OH)2D3.

Animals↗

Transthoracic aspiration needle biopsy: value in the diagnosis of pulmonary infections.

We reviewed 441 transthoracic needle aspiration biopsies to evaluate the use of the procedure in the diagnosis of pulmonary infections. Sixty-seven (15%) of the biopsies were performed because pulmonary infection was suspected. In these 67 cases, a specific diagnosis was made in 45 (67%). In 46 cases in which infection was ultimately found to be present, aspiration biopsy identified the organism in 35 (76%). Overall, clinically useful information was obtained in 54 (81%) of the 67 biopsies performed for pulmonary infection. In 369 biopsies performed for suspected malignant neoplasm, pulmonary infection was diagnosed in 13. The only significant complication was pneumothorax, which occurred in 18% of the biopsies. Chest tube placement was required in 5% of the biopsies. We conclude that transthoracic aspiration needle biopsy is of value in the diagnosis of suspected pulmonary infections.

Adult↗